Background: Randomized controlled trials (RCTs) data demonstrate that sevoflurane postconditioning improves clinical outcomes of liver resection with inflow occlusion, presumably due to hepatocyte protection from ischemic injury. However, mechanisms remain unclear. This study examines liver biopsy samples obtained in an RCT of sevoflurane postconditioning to test the hypothesis that sevoflurane attenuates hepatocyte apoptosis.
Methods: Messenger ribonucleic acid (mRNA) of pro- and antiapoptotic regulators Bax and B-cell lymphoma 2 (Bcl2) was examined in hepatic biopsies obtained during the RCT. Hepatic stellate cells (HSCs) and hepatocytes were exposed to hypoxia/reoxygenation (H/R) in vitro to evaluate the effect of sevoflurane postconditioning on apoptosis. The role of HSC as a potential apoptosis trigger in hepatocytes through the production of reactive oxygen species induced by H/R was explored by transferring supernatants from H/R-exposed HSC to hepatocytes as target cells.
Results: In patients of the RCT, the Bax/Bcl2 mRNA ratio in liver tissue was markedly decreased in the sevoflurane arm (25% ± 21% reduction; P = .001). In vitro, H/R increased reactive oxygen species production in HSC by 33% ± 16% (P = .025), while it was abolished in the presence of sevoflurane (P < .001). In hepatocytes, caspase was minimally activated by H/R. However, incubation of hepatocytes with supernatants of HSC, previously exposed to H/R, increased caspase activity by 28% ± 13% (P < .001). When exposed to supernatants from HSC undergoing sevoflurane postconditioning, caspase activation in hepatocytes was reduced by 20% ± 9% (P < .001), similarly to the sevoflurane effect on the BAX/Bcl2 mRNA ratio in the liver samples.
Conclusions: The study shows that sevoflurane postconditioning affects apoptosis of hepatocytes after ischemia-reperfusion injury in patients. It also demonstrates that HSC may be the effector cells of sevoflurane protection.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1213/ANE.0000000000003692 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sevoflurane postconditioning mitigates neuronal hypoxic-ischemic injury via regulating reactive astrocytic STAT3 protein modification.
Chem Biol Interact
January 2025
Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, China. Electronic address:
Astrocyte activation plays a pivotal role in accelerating the cascade of neuroinflammation associated with the development of hypoxic-ischemic brain injury. This study aimed to investigate the mechanism by which sevoflurane postconditioning mitigates neuronal damage through astrocytes by regulating reactive astrocytic Signal Transducer and Activator of Transcription 3 (STAT3) modifications. A modified Rice‒Vannucci model in rats and a conditioned culture system established by subjecting primary astrocytes to oxygen glucose deprivation, followed by using the conditioned medium to culture the neuron cell line SH-SY5Y were used to simulate HI insult in vivo and in vitro, respectively.
View Article and Find Full Text PDFSevoflurane Postconditioning Protects From an Early Neurological Deficit After Subarachnoid Hemorrhage: Results of a Randomized Laboratory Study in Rats.
Anesth Analg
November 2024
From the Institute of Physiology, University of Zurich, Zurich, Switzerland.
Background: Subarachnoid hemorrhage (SAH) is associated with neurocognitive impairment. Recent data suggest that sevoflurane attenuates edema formation after SAH in rats. However, so far, no information is available about the long-term repair phase, nor if sevoflurane impacts functionality by increasing vascularity.
View Article and Find Full Text PDFProtective effect of sevoflurane on myocardial ischemia-reperfusion injury: a systematic review and meta-analysis.
Int J Surg
November 2024
Physiology Research Center, Iran University of Medical Sciences, Tehran.
Article Synopsis
- Myocardial ischemia-reperfusion (I/R) injury can lead to serious heart problems during and after surgeries, and sevoflurane is thought to help protect the heart, though its effectiveness needs more clarity.
- A systematic review analyzed 51 studies involving over 8000 animal subjects to evaluate how sevoflurane pretreatment, preconditioning, and post-conditioning affect heart health in the context of I/R injury.
- Results indicated that sevoflurane significantly reduced heart damage, improved heart function, and lowered markers of injury, suggesting it could be a beneficial anesthetic during surgeries to mitigate I/R injury.
Sevoflurane: an opportunity for stroke treatment.
Med Gas Res
December 2024
Brain and Nerve Research Laboratory, Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
In developed countries, stroke is the leading cause of death and disability that affects long-term quality of life and its incidence is increasing. The incidence of ischemic stroke is much higher than that of hemorrhagic stroke. Ischemic stroke often leads to very serious neurological sequelae, which severely reduces the patients' quality of life and becomes a social burden.
View Article and Find Full Text PDFSevoflurane postconditioning attenuates cardiomyocytes hypoxia/reoxygenation injury via PI3K/AKT pathway mediated HIF-1α to regulate the mitochondrial dynamic balance.
BMC Cardiovasc Disord
May 2024
The First Affiliated Hospital of Xinjiang Medical University, 393 Xinyi Road, Xinjiang Uygur Autonomous Region, Urumqi, 830000, China.
Background: Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane postconditioning (SpostC), which attenuates I/R injury and exerts cardioprotective effects, regulates mitochondrial dynamic balance via HIF-1α, but the exact mechanism is unknown. This study investigates whether the PI3K/AKT pathway in SpostC regulates mitochondrial dynamic balance by mediating HIF-1α, thereby exerting myocardial protective effects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!